Metabonomic Strategy for the Evaluation of Chinese Medicine Salvia miltiorrhiza and Dalbergia odorifera Interfering with Myocardial Ischemia/Reperfusion Injury in Rats.

Extract of Salvia miltiorrhiza and Dalbergia Odorifera (SM-DOO) has been traditionally used for the prevention and treatment of cardiovascular diseases. However, information regarding the pharmacodyamic material basis and potential mechanism remain unknown. Male Sprague-Dawley rats were divided into four groups: Sham, Model, Diltiazem, and SM-DOO group, n = 6. Rats were pretreated with homologous drugs for 7 days, and then subjected to 30 minutes of ischemia followed by 180 minutes of reperfusion. Cardioprotection effects of SM-DOO on myocardial ischemia/reperfusion (MI/R) injury rats were examined by hemodynamics, infarct area, histopathology, biochemical indicators, and Western blot analysis. Metabonomics technology was further performed to evaluate the endogenous metabolites profiling systematically. According to the results of pattern recognition analysis, a clear separation of MI/R injury in the Model group and Sham group was achieved and SM-DOO pretreatment group was located much closer to the Sham group than the Model group, which was consistent with results of biochemistry and histopathological assay. Moreover, potential biomarkers were identified to elucidate the drug mechanism of SM-DOO, which may be related with pathways of energy metabolism, especially tricarboxylic acid (TCA) cycle (citric acid) and β-oxidation of fatty acids (3-hydroxybutyric, palmitoleic acid, heptadecanoic acid, and arachidonic acid). In addition, the protein expressions of p-AMPK and p-ACC in the SM-DOO group were significantly elevated, while the levels of carnitine palmitoyl-CoA transferase-1 (CPT-1), p-PDK, and p-PDC were dramatically reduced by SM-DOO. In conclusion, SM-DOO pretreatment could ameliorate MI/R injury by intervening with energy metabolism, especially TCA cycle and β-oxidation of fatty acids. This work showed that the metabonomics method combinate with conventional pharmacological methods is a promising tool in the efficacy and mechanism research of traditional Chinese medicines.